Exposure of cyclosporin a in whole blood, cerebral spinal fluid, and brain extracellular fluid dialysate in adults with traumatic brain injury

Gretchen M. Brophy, Anna Teresa Mazzeo, Satjit Brar, Oscar Luis Alves, Kristen Bunnell, Charlotte Gilman, Tom Karnes, Ron L. Hayes, Ross Bullock

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cyclosporin A (CsA), an immunosuppressive medication traditionally used in the prevention of post-transplant rejection, is a promising neuroprotective agent for traumatic brain injury (TBI). Preliminary studies in animals and humans describe the efficacy and safety of CsA when administered following neurotrauma. The objective of this study is to describe CsA exposure in adults with severe TBI by assessing concentrations in whole blood, cerebrospinal fluid (CSF), and brain extracellular fluid (ECF) dialysate as measured by brain microdialysis. Severe TBI patients were enrolled in a randomized controlled trial following the written informed consent of their legal guardians. Patients received either CsA 5 mg/kg as a continuous infusion over 24 h, or matching placebo. Noncompartmental exposure analyses were performed using CsA concentrations in whole blood, CSF, and ECF dialysate. There were 37 patients randomized to the CsA arm of the trial and included in this exposure analysis. CsA was detected in the ECF dialysate and CSF at a fraction of the whole blood concentration. Mean CsA maximum concentrations were achieved at 24 and 30 h from the start of the 24 h infusion, in the CSF and ECF dialysate, respectively. A correlation was found between ECF dialysate and CSF concentrations. CsA was detected in the blood, CSF, and brain ECF dialysate. CsA exposure characteristic differences exist for whole blood, CSF, and ECF dialysate in severe TBI patients when administered as a continuous intravenous infusion. These exposure characteristics should be used for safer CsA dose optimization to achieve target CsA concentrations for neuroprotection in future TBI studies.

Original languageEnglish (US)
Pages (from-to)1484-1489
Number of pages6
JournalJournal of neurotrauma
Volume30
Issue number17
DOIs
StatePublished - Sep 1 2013

Keywords

  • Cyclosporin
  • Neuroprotection
  • TBI

ASJC Scopus subject areas

  • Clinical Neurology

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    Brophy, G. M., Mazzeo, A. T., Brar, S., Alves, O. L., Bunnell, K., Gilman, C., Karnes, T., Hayes, R. L., & Bullock, R. (2013). Exposure of cyclosporin a in whole blood, cerebral spinal fluid, and brain extracellular fluid dialysate in adults with traumatic brain injury. Journal of neurotrauma, 30(17), 1484-1489. https://doi.org/10.1089/neu.2012.2524